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Salmonella enterica serovar Typhimurium is a facultative intracellular pathogen that infects humans and animals. Survival and growth in host macrophages represents a crucial step for S . Typhimurium virulence. Many genes that are essential for S . Typhimurium proliferation in macrophages and associated with virulence are highly expressed during the intracellular lifecycle. yaeB , which encodes an RNA methyltransferase, is also upregulated during S . Typhimurium growth in macrophages. However, the involvement of YaeB in S . Typhimurium pathogenicity is still unclear. In this study, we investigated the role of YaeB in S . Typhimurium virulence. Deletion of yaeB significantly impaired S . Typhimurium growth in macrophages and virulence in mice. The effect of yaeB on pathogenicity was related to its activation of pstSCAB , a phosphate (P i )-specific transport system that is verified here to be important for bacterial replication and virulence. Moreover, qRT-PCR data showed YaeB was induced by the acidic pH inside macrophages, and the acidic pH passed to YeaB through inhibiting global regulator histone-like nucleoid structuring (H-NS) which confirmed in this study can repress the expression of yaeB . Overall, these findings identified a new virulence regulatory network involving yaeB and provided valuable insights to the mechanisms through which acidic pH and low P i regulate virulence.

YaeB, Expressed in Response to the Acidic pH in Macrophages, Promotes Intracellular Replication and Virulence of Salmonella Typhimurium